Anticorrosion system capable of being used for wound surface as well as preparation method and application of anticorrosion system

Abstract

The invention discloses an anti-corrosion system for a wound surface as well as a preparation method and application of the anti-corrosion system. The anticorrosion system is prepared from 0.4 to 0.8 weight percent of p-hydroxyacetophenone, 10 to 15 weight percent of capryloyl hydroximic acid, 0.8 to 1.2 weight percent of glycerol caprylate, 25 to 50 weight percent of polyhydric alcohol and the balance of purified water. The anti-corrosion system adopts non-traditional anti-corrosion components, has excellent antibacterial performance and low cytotoxicity, and has a wide application prospect in passive second-class medical equipment products.

Description

Technical Field

[0001] This invention belongs to the field of medical device technology, specifically relating to an antiseptic system that can be used on wounds, its preparation method, and its application. Background Technology

[0002] With the booming development of the medical aesthetics industry, more and more people are choosing to improve their appearance and boost their self-confidence through medical aesthetic procedures. However, this often results in localized skin damage or wounds. In the field of medical device technology, wound management has always been a crucial aspect. Whether caused by medical aesthetic procedures or accidental injuries, wounds face multiple challenges, including redness, infection, delayed healing, and scarring. Infection, in particular, not only prolongs the patient's recovery period but can also lead to serious complications and even endanger life. In recent years, driven by consumer demand, Class II passive medical device products targeting localized skin damage or wounds have gradually emerged, including medical repair dressings, liquid sprays, and gels. Therefore, developing safe and easy-to-use wound antiseptic systems for these products is of great significance for reducing irritation, promoting wound healing, minimizing complications, and improving consumers' quality of life.

[0003] In Class II passive medical devices that are neither completely sterile nor partially sterile, appropriate preservatives are required depending on the product's specific function. The main purpose is to prevent microbial contamination of the feed solution in sterile products during production and filling, or to maintain the microbial count within the technical requirements for non-sterile products during their effective shelf life. While commonly used preservatives can inhibit microbial growth, some components may damage normal tissue cells, affecting wound healing. Furthermore, during registration, biological indicators of the product must be tested, with cytotoxicity and pyrogen levels having high requirements. Therefore, registering traditional preservatives as components of medical devices presents certain challenges. Summary of the Invention

[0004] To address the issue of traditional preservatives failing to meet the application requirements for micro-wounds or inflammatory reactions on the skin after cosmetic procedures, this invention provides a wound-preserving system, its preparation method, and its application. This invention, through screening and compounding various non-traditional preservatives and adjusting the proportions of each component, prepares a non-traditional preservative system with low cytotoxicity and good antiseptic effect. This system minimizes irritation to wounds and normal cells while possessing broad-spectrum antibacterial properties, meeting the needs of registered ingredients and market consumers. It is suitable for use in Class II medical device products, thereby achieving an overall repair effect.

[0005] The technical solution of the present invention is as follows:

[0006] The antiseptic system that can be used on wounds consists of the following components by weight percentage: 0.4-0.8 wt% p-hydroxyacetophenone, 10-15 wt% capryloyl hydroxamic acid, 0.8-1.2 wt% glyceryl caprylate, 25-50 wt% polyol, and the balance being purified water.

[0007] Furthermore, the polyol is selected from one or more of 1,3-butanediol, 1,2-hexanediol, and 1,2-pentanediol.

[0008] Furthermore, the above-mentioned preservative system, by mass percentage, consists of the following components: 0.6 wt% p-hydroxyacetophenone, 13 wt% capryloyl hydroxamic acid, 1 wt% glyceryl caprylate, 40 wt% 1,3-butanediol, with the balance being purified water.

[0009] The preparation method of the above-mentioned preservative system is as follows: according to the ratio, p-hydroxyacetophenone is first added to the polyol and dissolved under water bath heating and stirring at 70±5℃. Then, octanoyl hydroxamic acid and glyceryl octanoate are added in sequence and stirred to mix them thoroughly. Then, purified water is added and stirred until the mixture is uniform. The mixture is then cooled to room temperature to obtain the preservative system.

[0010] The present invention also provides the application of the above-mentioned anti-corrosion system in passive Class II medical device products.

[0011] Furthermore, passive Class II medical device products include, but are not limited to, adhesive dressings, liquid dressings, and gel formulations.

[0012] Furthermore, in passive Class II medical device products, the amount of anti-corrosion system added is 7-10 wt%.

[0013] Furthermore, the present invention provides a liquid dressing, which, by weight percentage, comprises the following components: 0.1 wt% sodium hyaluronate, 0.05 wt% recombinant collagen, 0.5 wt% trehalose, 3 wt% glycerin, 8 wt% preservative system, 0.001 wt% disodium hydrogen phosphate, and the balance being purified water.

[0014] The method for preparing the above-mentioned liquid dressing includes the following steps:

[0015] (1) Under stirring, slowly add sodium hyaluronate to an appropriate amount of purified water, keep the temperature constant at 80±5℃ for 5 to 10 minutes, then cool to below 40℃ and stop stirring, as phase A;

[0016] (2) Add recombinant collagen, trehalose and glycerol to an appropriate amount of purified water and stir until completely dissolved to form phase B;

[0017] (3) Add phase B to phase A, stir until evenly mixed, then add the anti-corrosion system and continue stirring until evenly mixed;

[0018] (4) Add disodium hydrogen phosphate to the mixing system in step (3) to make the pH of the mixture liquid 5.5 to 7.0, add purified water to make up to 100 wt%, and obtain liquid dressing.

[0019] Compared with the prior art, the present invention has the following advantages:

[0020] (1) The antiseptic system of the present invention is a non-traditional antiseptic system. It causes less damage to normal tissue cells and has less impact on the wound healing process. It does not conflict with other components in passive Class II medical device products. It can still be used when the skin is damaged. At the same time, it meets the requirements of common registered components of Class II medical devices and can be applied to medical device products of different dosage forms and repair purposes.

[0021] (2) The combination of multiple preservatives in this invention enhances the broad spectrum of antibacterial activity, ensuring that the number of microorganisms can be controlled below the standard during production and shelf life. It can also pass the high requirements of cytotoxicity, pyrogen and other tests in the biological testing projects for medical device registration. Liquid dressings using the preservative system of this invention will not cause allergies, redness and stinging when in contact with the skin as a spray or smear. It has broad application prospects in passive Class II medical device products. Detailed Implementation

[0022] To make the technical solution of the present invention clearer and easier to understand, the technical solution of the present invention will be clearly and completely described below in conjunction with specific embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0023] Example 1

[0024] 1. A preservative system, comprising, by mass percentage: 0.6 wt% p-hydroxyacetophenone, 13 wt% capryloyl hydroxamic acid, 1 wt% glyceryl caprylate, 40 wt% 1,3-butanediol, with the balance being purified water; prepared by the following steps: p-hydroxyacetophenone is added to 1,3-butanediol according to the specified ratio, heated in a water bath at 70±5°C and stirred until dissolved, then capryloyl hydroxamic acid and glyceryl caprylate are added sequentially, and stirred until fully mixed to obtain the preservative system.

[0025] 2. A liquid dressing, by weight percentage, comprises the following components: 0.1 wt% sodium hyaluronate, 0.05 wt% recombinant collagen, 0.5 wt% trehalose, 3 wt% glycerin, 8 wt% of the above-mentioned preservative system, 0.001 wt% disodium hydrogen phosphate, and the balance being purified water; prepared by the following steps:

[0026] (1) Add an appropriate amount of purified water to a beaker, turn on the stirrer at 500 r / min, slowly add sodium hyaluronate to the beaker, turn on the water bath heating, keep the temperature constant at 80℃ for 5 min, then turn off the heating, and turn off the stirring when the temperature of the liquid drops to 40℃ or below, which is the A phase.

[0027] (2) In another suitable beaker, add recombinant collagen, trehalose and glycerol, then add an appropriate amount of purified water, and stir manually at room temperature until completely dissolved, as phase B;

[0028] (3) Add phase B to phase A, turn on the stirrer at 500 r / min, stir for 5 min, add the anti-corrosion system, and continue stirring for 3 min to make it evenly mixed;

[0029] (4) Add disodium hydrogen phosphate to the above mixture to make the pH of the mixture liquid 5.5 to 7.0, and add purified water to make up to 100 wt% to obtain liquid dressing.

[0030] Example 2

[0031] 1. A preservative system, comprising, by weight percentage: 0.4 wt% p-hydroxyacetophenone, 10 wt% capryloyl hydroxamic acid, 0.8 wt% glyceryl caprylate, 25 wt% 1,2-hexanediol, with the balance being purified water. The preparation method is the same as in Example 1.

[0032] 2. A liquid dressing, substantially the same as in Example 1, except that the amount of antiseptic system added is 7 wt%.

[0033] Example 3

[0034] 1. A preservative system, comprising, by weight percentage: 0.8 wt% p-hydroxyacetophenone, 15 wt% capryloyl hydroxamic acid, 1.2 wt% glyceryl caprylate, 50 wt% 1,2-pentanediol, with the balance being purified water. The preparation method is the same as in Example 1.

[0035] 2. A liquid dressing, with the same components as in Example 1, except that the amount of the above-mentioned antiseptic system added is 10 wt%.

[0036] Comparative Example 1

[0037] 1. A preservative system, comprising, by weight percentage: 0.2 wt% p-hydroxyacetophenone, 8 wt% capryloyl hydroxamic acid, 0.6 wt% glyceryl caprylate, 20 wt% 1,3-butanediol, with the balance being purified water. The preparation method is the same as in Example 1.

[0038] 2. A liquid dressing, substantially the same as in Example 1, except that the above-described antiseptic system is added.

[0039] Comparative Example 2

[0040] 1. A preservative system, comprising, by weight percentage: 1 wt% p-hydroxyacetophenone, 18 wt% capryloyl hydroxamic acid, 1.5 wt% glyceryl caprylate, 55 wt% 1,3-butanediol, with the balance being purified water. The preparation method is the same as in Example 1.

[0041] 2. A liquid dressing, substantially the same as in Example 1, except that the above-described antiseptic system is added.

[0042] Comparative Example 3

[0043] 1. A preservative system, comprising, by weight percentage: 13 wt% capryloyl hydroxamic acid, 1 wt% glyceryl caprylate, 40% 1,3-butanediol, with the balance being purified water. The preparation method is the same as in Example 1.

[0044] 2. A liquid dressing, substantially the same as in Example 1, except that the above-described antiseptic system is added.

[0045] Comparative Example 4

[0046] 1. A preservative system, comprising, by weight percentage: 0.6 wt% p-hydroxyacetophenone, 1 wt% glyceryl caprylate, 40% 1,3-butanediol, with the balance being purified water. The preparation method is the same as in Example 1.

[0047] 2. A liquid dressing, substantially the same as in Example 1, except that the above-described antiseptic system is added.

[0048] Comparative Example 5

[0049] 1. A preservative system, comprising, by weight percentage: 0.6 wt% p-hydroxyacetophenone, 13 wt% octanoyl hydroxamic acid, 40% 1,3-butanediol, with the balance being purified water. The preparation method is the same as in Example 1.

[0050] 2. A liquid dressing, substantially the same as in Example 1, except that the above-described antiseptic system is added.

[0051] Comparative Example 6

[0052] 1. A preservative system, comprising, by weight percentage: 0.6 wt% p-hydroxyacetophenone, 13 wt% capryloyl hydroxamic acid, 1 wt% glyceryl caprylate, and the balance being purified water. The preparation method is the same as in Example 1.

[0053] 2. A liquid dressing, substantially the same as in Example 1, except that the above-described antiseptic system is added.

[0054] Performance test examples

[0055] 1. Antibacterial efficacy test

[0056] The liquid dressings prepared in Examples 1-3 and Comparative Examples 1-6 were tested for antibacterial efficacy according to the 2025 edition of the Chinese Pharmacopoeia, Volume IV, Method 1121, for antibacterial efficacy testing. The specific methods are as follows:

[0057] Bacterial and fungal suspensions were prepared separately, including Staphylococcus aureus [CMCC(B)26003], Pseudomonas aeruginosa [CMCC(B)10104], Candida albicans [CMCC(F)98001], and Aspergillus niger [CMCC(F)98003], with the bacterial suspension concentration being 10. 8 cfu / ml, fungal concentration 10 8 cfu / ml; Each example and comparative sample was transferred to four suitable sterile containers, and each container was inoculated with one test bacterium. The bacterial load per 1g of liquid dressing sample was 10. 5 ~10 6 The volume of the inoculated bacterial solution should not exceed 1% of the volume of the liquid dressing sample. Mix thoroughly to ensure uniform distribution of the test bacteria, then store at 20–25°C in the dark. The viability of each bacterium is measured at 2, 7, 14, and 28 days after inoculation. Take 1g of sample solution from each container and determine the number of bacteria in each sample. Based on the viable bacterial count, calculate the number of each test bacterium added to 1g of sample solution and the number of bacteria at each time interval, and convert this to a lg value. The evaluation criteria for the antibacterial efficacy of the sample solution are shown in Table 1. "Reduced lg value" refers to the difference between the lg value of the bacterial count measured at each time interval and the lg value of the inoculated bacterial count in 1g of sample solution.

[0058] In the table, "A" refers to the required antibacterial efficacy standard. In special cases, such as when the antibacterial agent may increase the risk of adverse reactions, the antibacterial efficacy standard of "B" should be met at least.

[0059] Table 1 Criteria for Judging the Antibacterial Efficacy of Dermal Drug Delivery Preparations

[0060]

[0061] Table 2. Antibacterial efficacy results of the examples and control examples.

[0062]

[0063]

[0064] 2. Cytotoxicity test

[0065] (1) Test method:

[0066] Liquid dressings prepared in Examples 1-3 and Comparative Examples 1-6 were subjected to in vitro cytotoxicity tests using the MTT assay as described in GB / T16886.5-2017 / ISO10993-5:2009 "Biological evaluation of medical devices - Part 5: In vitro cytotoxicity tests". The potential cytotoxicity of the samples to L929 mammalian fibroblasts was evaluated. The specific test methods are as follows:

[0067] L929 cells in the logarithmic growth phase were digested with trypsin, centrifuged, and the cell suspension was resuspended in fresh culture medium to obtain 1×10⁻⁶ cells / cells. 5 CFU / mL cell suspension. The suspension cells were seeded at 100 μL per well in 96-well plates and cultured in a cell culture incubator for 24 hours. After the cells formed a monolayer, the original culture medium was discarded.

[0068] Add 100 μL of sample extract (100%, 75%, 50%, 25%), blank control sample, and positive control sample (0.1% ZDEC) to the corresponding wells of a 96-well plate, with 5 replicates per group. After incubating the 96-well plate in a cell culture incubator for 24 hours, observe the cell morphology. Then remove the liquid, add 50 μL of MTT (1 mg / ml) to each well, incubate for 2 hours, remove the supernatant, add 100 μL of DMSO to each well to dissolve the crystals, and measure the absorbance at 570 nm wavelength on a microplate reader. Calculate the cytotoxicity of each sample using the formula: Cell viability % = Sample (or positive) group / Blank control group × 100%.

[0069] (2) Evaluation criteria for cytotoxicity:

[0070] The cell viability of a 50% sample extract should be the same or higher than that of a 100% sample extract; otherwise, the test should be repeated. The lower the percentage of cell viability, the greater the potential cytotoxicity. If the cell viability is <70%, the sample has potential cytotoxicity. The cell viability under the action of the sample extract is based on the 100% extract. If the positive control does not cause cytotoxicity, the test does not meet the acceptance criteria.

[0071] Table 3. Cytotoxicity results of samples from the examples and control cases.

[0072]

[0073]

[0074]

[0075] Based on the test results in Tables 2 and 3, the liquid dressing samples of Examples 1-3 all exhibited satisfactory antibacterial efficacy, showing inhibitory effects against common bacteria and fungi. Both antibacterial efficacy and cytotoxicity increased with increasing concentration. However, no significant cytotoxicity was observed against L929 mammalian fibroblasts, suggesting minimal irritation to damaged skin, making them suitable for use in medical devices for wounds. Comparative Examples 1-6 show that when a certain component is missing from the preservative system of this invention, although cytotoxicity decreases, the antibacterial effect is reduced to varying degrees, failing to achieve the intended preservative purpose. With the components remaining constant, low concentrations of each component in the preservative system result in substandard antibacterial efficacy. Higher concentrations of each component increase antibacterial efficacy, but also increase cytotoxicity, exhibiting relatively significant cytotoxicity. Example 1 shows the best balance between antibacterial and cytotoxic effects. In summary, the preservative system of the present invention can achieve a relative balance between antibacterial and cytotoxic effects, while meeting the registration requirements. The concentration can be selected according to the dosage form and use of the actual product to achieve a suitable effect.

[0076] 3. Human skin irritation test

[0077] Samples of the liquid dressings from Examples 1-3 were taken, and volunteers were recruited to conduct skin irritation perception tests. The aim was to verify the product's irritation level in actual use based on theoretical results. The specific test methods are as follows:

[0078] Fifteen subjects with sensitive skin, weak skin barrier prone to redness, or who had recently undergone cosmetic procedures were randomly recruited. Among them, there were 3 males and 12 females, aged 22-55 years. The liquid dressing samples of Examples 1-3 and the negative control (sterile saline) were all placed into spray bottles that had been cleaned and dried beforehand. After each subject washed and dried their face with room temperature water, the sample was sprayed evenly onto their face. Every 1 hour (after the sample liquid had dried), the face was washed again and the next sample spray was tested. The subjects were asked to score each sample spray according to the established scoring criteria.

[0079] Table 4 Scoring criteria for skin irritation test

[0080] Skin irritation Evaluation score Negative reaction, no obvious reaction 0 points A slight swelling sensation, without redness, swelling, or stinging pain. 1 point There is a noticeable feeling of swelling, with local redness and swelling, but no stinging pain. 2 points There is a noticeable feeling of swelling and pain, with significant redness and swelling, and a slight stinging sensation in the affected area. 3 points Extensive redness, swelling, and pain, with noticeable stinging. 4 points

[0081] Table 5 Results of skin irritation test

[0082]

[0083]

[0084] Table 5 shows that most of the 15 subjects rated the irritation level of the test sample as 0, indicating no significant reaction and almost no skin irritation, which is basically consistent with the cytotoxicity test results. In Example 3, one person reported a slight swelling sensation, which may be related to the high concentration of preservative, insufficient matching of the product dosage form, or individual skin perception bias. As a liquid dressing, this product can achieve the desired effect with a lower preservative concentration within the selection range, and is more suitable. Therefore, the preservative system of this invention can be applied to medical device products of various dosage forms, meeting consumers' high requirements for wound care products and registration testing, and has high practical application value in production.

[0085] The sample forms and addition ratios used in the above experiments are merely typical embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations and substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A wound-preserving system, characterized in that, By weight percentage, it consists of the following components: 0.4-0.8 wt% p-hydroxyacetophenone, 10-15 wt% capryloyl hydroxamic acid, 0.8-1.2 wt% glyceryl caprylate, 25-50 wt% polyol, and the balance being purified water.

2. The anti-corrosion system according to claim 1, characterized in that, The polyol is selected from one or more of 1,3-butanediol, 1,2-hexanediol and 1,2-pentanediol.

3. The anti-corrosion system according to claim 1, characterized in that, By weight percentage, it consists of the following components: 0.6 wt% p-hydroxyacetophenone, 13 wt% capryloyl hydroxamic acid, 1 wt% glyceryl caprylate, 40 wt% 1,3-butanediol, with the balance being purified water.

4. The method for preparing the anti-corrosion system according to any one of claims 1 to 3, characterized in that, The specific steps are as follows: According to the ratio, first add p-hydroxyacetophenone to the polyol and dissolve it under water bath heating and stirring at 70±5℃. Then add octanoyl hydroxamic acid and glyceryl caprylate in sequence, stir to mix them thoroughly and evenly, add purified water, stir until they are mixed evenly, and cool to room temperature to obtain the preservative system.

5. The application of the anti-corrosion system according to claim 4 in passive Class II medical device products.

6. The application according to claim 5, characterized in that, Passive Class II medical device products are adhesive dressings, liquid dressings, or gel-based dosage forms.

7. The application according to claim 6, characterized in that, In passive Class II medical device products, the amount of anti-corrosion system added is 7~10wt%.

8. A liquid dressing, characterized in that, The product comprises, by weight percentage, the following components: 0.1 wt% sodium hyaluronate, 0.05 wt% recombinant collagen, 0.5 wt% trehalose, 3 wt% glycerol, 8 wt% of the preservative system as described in any one of claims 1 to 3, 0.001 wt% disodium hydrogen phosphate, and the balance being purified water.

9. The method for preparing the liquid dressing according to claim 8, characterized in that, Includes the following steps: (1) Under stirring, slowly add sodium hyaluronate to an appropriate amount of purified water, keep the temperature constant at 80±5℃ for 5~10min, then cool to below 40℃ and stop stirring, as phase A; (2) Add recombinant collagen, trehalose and glycerol to an appropriate amount of purified water and stir until completely dissolved to form phase B; (3) Add phase B to phase A, stir until evenly mixed, then add the anti-corrosion system and continue stirring until evenly mixed; (4) Add disodium hydrogen phosphate to the mixing system in step (3) to make the pH of the mixture liquid 5.5~7.0, add purified water to make up to 100wt%, and obtain liquid dressing.

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